CN102553441B - Micro-dialysis device - Google Patents

Micro-dialysis device Download PDF

Info

Publication number
CN102553441B
CN102553441B CN201210014783.XA CN201210014783A CN102553441B CN 102553441 B CN102553441 B CN 102553441B CN 201210014783 A CN201210014783 A CN 201210014783A CN 102553441 B CN102553441 B CN 102553441B
Authority
CN
China
Prior art keywords
layer
wall surface
film
mass density
hole dimension
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201210014783.XA
Other languages
Chinese (zh)
Other versions
CN102553441A (en
Inventor
B·克劳泽
H·戈尔
M·霍尔农
C·克拉夫特
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Gambro Lundia AB
Original Assignee
Gambro Lundia AB
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gambro Lundia AB filed Critical Gambro Lundia AB
Publication of CN102553441A publication Critical patent/CN102553441A/en
Application granted granted Critical
Publication of CN102553441B publication Critical patent/CN102553441B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/66—Polymers having sulfur in the main chain, with or without nitrogen, oxygen or carbon only
    • B01D71/68—Polysulfones; Polyethersulfones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/02—Hollow fibre modules
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/08—Hollow fibre membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/08—Hollow fibre membranes
    • B01D69/087—Details relating to the spinning process
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/08—Hollow fibre membranes
    • B01D69/087—Details relating to the spinning process
    • B01D69/0871—Fibre guidance after spinning through the manufacturing apparatus
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/44—Polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds, not provided for in a single one of groups B01D71/26-B01D71/42
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/44—Polymers obtained by reactions only involving carbon-to-carbon unsaturated bonds, not provided for in a single one of groups B01D71/26-B01D71/42
    • B01D71/441—Polyvinylpyrrolidone
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/58—Other polymers having nitrogen in the main chain, with or without oxygen or carbon only
    • B01D71/62—Polycondensates having nitrogen-containing heterocyclic rings in the main chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue
    • A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using microdialysis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2323/00—Details relating to membrane preparation
    • B01D2323/06—Specific viscosities of materials involved
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2323/00—Details relating to membrane preparation
    • B01D2323/08—Specific temperatures applied
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2323/00—Details relating to membrane preparation
    • B01D2323/08—Specific temperatures applied
    • B01D2323/081—Heating
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2323/00—Details relating to membrane preparation
    • B01D2323/12—Specific ratios of components used
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2323/00—Details relating to membrane preparation
    • B01D2323/219—Specific solvent system
    • B01D2323/22—Specific non-solvents or non-solvent system
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/022—Asymmetric membranes

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Separation Using Semi-Permeable Membranes (AREA)
  • External Artificial Organs (AREA)
  • Artificial Filaments (AREA)
  • Spinning Methods And Devices For Manufacturing Artificial Fibers (AREA)

Abstract

The present invention relates to a kind of semipermeable hallow fibre film, its inner chamber that there is outer wall surface, inner wall surface and extend along its length, and the outer wall surface being less than 10nm in surface roughness has selective layer.According to film of the present invention, there is in outer wall surface minimum hole dimension, in nanoscale Smooth, continuous and uniform outer wall surface, and the different layers of 4 or 5 different hole dimensions and density.In addition the present invention relates to preparation method and the purposes of described film.

Description

Micro-dialysis device
Technical field
The application is application number is 200780039131.9, the applying date be October 11 in 2007 day, be called the divisional application of the patent application of " hollow-fibre membrane and preparation method thereof ".
The present invention relates to a kind of semipermeable hallow fibre film of inner chamber that there is outer wall surface, inner wall surface and extend along its length.Relate more specifically to the film that outer wall surface has selective layer.The invention further relates to the micro-dialysis device using this film.
Background of invention
Semipermeable hallow fibre film is known in detail in such as EP-A-0568045, EP-A-0168783, EP-B-0082433, WO86/00028 and EP0824960.These films are obtained by polymeric synthetic material, and they have the unsymmetric structure (gap) of high diffusivity permeability, and have the drainage capacity from small throughput to the ultrafiltration of high flux scope.In EP-A-0305787, disclose 3-tier architecture film and the filter with respective performances.
Film according to prior art does very well, but still some spaces that there is improvement and optimize.
A restricted feature of these films is that fluid to be filtered flows in the inner chamber of hollow membrane, and filtrate from lumen side by fibre wall to outer wall side.In order to not by these filter contamination or blocking, the size of doughnut such as interior diameter, wall thickness etc. must even as big as allowing good in doughnut chamber and flowing at a high speed.
In DE19913416, advise the filtration carried out from outside to inside, namely outside has selective layer.
But, when processing body fluid as blood, the most important thing is smooth as far as possible with the film surface of bioresorbable, there is low-protein absorption, high-biocompatibility and low blood coagulation activity (thrombogenicity).
Invention describes
The present invention relates to a kind of semipermeable hallow fibre film, its inner chamber that there is outer wall surface, inner wall surface and extend along its length, and in outer wall surface, there is selective layer.According to the present invention, film has minimum hole dimension in outer wall surface, and its outer wall surface at nanoscale Smooth, continuously and evenly, roughness parameter R aand R qbe not more than 10nm and substantially there is no roughness; This roughness utilizes AFM (AFM) to measure, and utilizes equation below to calculate roughness parameter R aand R q:
R a = 1 N Σ i = 1 N | Z i | R q = 1 N Σ i = 1 N Z i 2
Wherein N is data point sum, Z ithe height of data point more than the average image plane (averagepicturelevel).With the outer surface that this is smooth, and in conjunction with polymeric system used and film formation condition, achieve the low blood coagulation activity of film.If extremely smooth surface directly contacts use with blood, inhibit haemolysis.Haemocyte with the contact process of smooth surface in do not break.This slickness also reduces with the interaction of protein and protein adsorption on the outer surface of hollow-fibre membrane.
In one embodiment, doughnut membranous wall has hole dimension at least 4 layer different with mass density, wherein has the hole dimension less than 2 layers of direct neighbor on both sides inside and outside this layer and high mass density apart from nearest layer in the middle of fibre wall.With this structure, the physical stability of film is maintained, even if film has little interior diameter and little wall thickness.It also allows density of texture and hole dimension by changing outer and intermediate layer to regulate stalling characteristic, namely retains (cut-off) and hydraulic diffusibility.
In another embodiment, doughnut membranous wall has hole dimension 4 layer different with mass density.Ground floor, in outer wall surface, has minimum hole dimension and the highest mass density.The second layer adjoins ground floor and is arranged on the inside side of ground floor, and it has the hole dimension larger than ground floor and low mass density.Third layer adjoins the second layer and is arranged on the inside side of the second layer, and it has the hole dimension less than the second layer and high mass density but the hole dimension larger than ground floor and low mass density.4th layer in inner wall surface, adjacent third layer and be arranged on the inside side of third layer, it has the hole dimension larger than ground floor, the second layer and third layer and low mass density.The degree of opening of hollow fiber cavity side can be increased, if this provide the possibility needing to improve diffusion hereditary property with this structure.And the flowing of eddy current shape fluid can directly realize in lumen side, this is favourable to material Transfer phenomenon.
In another embodiment, doughnut membranous wall has hole dimension 5 layer different with mass density.Ground floor, in outer wall surface, has minimum hole dimension and the highest mass density.The second layer adjoins ground floor and is arranged on the inside side of ground floor, and it has the hole dimension larger than ground floor and low mass density.Third layer adjoins the second layer and is arranged on the inside side of the second layer, and it has the hole dimension less than the second layer and high mass density but the hole dimension larger than ground floor and low mass density.4th layer of adjacent third layer and be arranged on the inside side of third layer, it has the hole dimension larger than ground floor, the second layer and third layer and low mass density.Layer 5 is in inner wall surface, and adjoin the 4th layer and be arranged on the 4th layer of inside side, it has than ground floor, the second layer, third layer and the 4th layer of large hole dimension and low mass density.The degree of opening of hollow fiber cavity side can be increased, if this provide the possibility needing to improve diffusion hereditary property with this structure.And the flowing of eddy current shape fluid can directly realize in lumen side, this is favourable to material Transfer phenomenon.
In another embodiment, doughnut membranous wall has hole dimension 5 layer different with mass density.Ground floor, in outer wall surface, has minimum hole dimension and the highest mass density.The second layer adjoins ground floor and is arranged on the inside side of ground floor, and it has the hole dimension larger than ground floor and low mass density.Third layer adjoins the second layer and is arranged on the inside side of the second layer, and it has the hole dimension less than the second layer and high mass density but the hole dimension larger than ground floor and low mass density.4th layer of adjacent third layer and be arranged on the inside side of third layer, it has the hole dimension larger than ground floor, the second layer and third layer and low mass density.Layer 5 is in inner wall surface, and adjoin the 4th layer and be arranged on the 4th layer of inside side, it has than the 4th layer of little hole dimension and high mass density.For this structure, inner surface also can have smooth inner surface, and this is needs when two kinds of fluid systems that highly may pollute transmit in the inner side and outer side of hollow-fibre membrane respectively.Smooth inner surface reduces haemolysis risk (when contacting blood) and surface contamination the risk of adsorbent.In addition, can by meticulous adjustment internal layer form, namely structure regulates diffusion and convection current transmission (convectivetransport) character.Due to this Rotating fields, engineering properties can improve further.
In another embodiment, the hydraulic diffusibility of hollow-fibre membrane is 1 × 10 -4~ 100 × 10 -4[cm 3/ cm 2× bar × s], preferably 1 × 10 -4~ 70 × 10 -4[cm 2/ cm 2× bar × s], most preferably 1 × 10 -4~ 27 × 10 -4[cm 3/ cm 2× bar × s].With this hydraulic diffusibility, for molecular dimension (according to fluid and measuring condition 100,000 dalton at the most) or molecular shape, reach minimum by the convection current transmission of membranous wall, there is the high diffusivity transmission of wide region simultaneously.
In another embodiment, hollow-fibre membrane comprises the polymer composition containing polysulfones (PSU), polyether sulfone (PES) or poly arylene ether sulfone (PAES) and PVP (PVP).
In even another embodiment, PVP (PVP) in film comprises the blend of at least two kinds of PVPs (PVP) homopolymers, wherein a kind of homopolymers has 10,000g/mol ~ 100,000g/mol, the preferably average relative molecular mass of 30,000g/mol ~ 60,000g/mol (=low-molecular-weight PVP), another kind of homopolymers has 500,000g/mol ~ 2,000,000g/mol, preferably 800,000g/mol ~ 2, the average relative molecular mass of 000,000g/mol (=HMW PVP).
In one embodiment, doughnut membranous wall has 50 ~ 2000 μm, preferably the interior diameter of 104 ~ 1464 μm.
In one embodiment, doughnut membranous wall has 10 ~ 200 μm, preferably the wall thickness of 22 ~ 155 μm.
In another embodiment, doughnut membranous wall has for urea (60g/mol) is 4 × 10 -6~ 15 × 10 -6cm 2the cross-film effective diffusion cofficient of/second.
In addition, the present invention relates to a kind of method preparing semipermeable hallow fibre film, comprise and the outer ring slit of polymer solution by hollow fiber spinning nozzle is extruded, the endoporus of hole liquid by hollow fiber spinning nozzle is extruded simultaneously, enter precipitating bath.According to the present invention, polymer solution comprises 10 ~ 20 % by weight polysulfones (PSU), polyether sulfone (PES) or poly arylene ether sulfone (PAES), 2 ~ 15 % by weight PVP (PVP) and solvents; Hole liquid comprises 50 ~ 75 % by weight solvents and 25 ~ 50 % by weight water; Precipitating bath comprises 50 ~ 70 % by weight solvents and 30 ~ 50 % by weight water and has the temperature of 22 ~ 31 DEG C, and the distance between the exhaust outlet of hollow fiber spinning nozzle and precipitating bath surface is 0 ~ 10cm.
According in a kind of embodiment of the inventive method, precipitating bath comprises 52 ~ 69 % by weight solvents and 31 ~ 48 % by weight water.
According in another embodiment of the inventive method, the solvent in polymer solution, hole liquid and precipitating bath is selected from 1-METHYLPYRROLIDONE, N-ethyl pyrrolidone, NOP, dimethylacetylamide, dimethyl formamide, dimethyl sulfoxide (DMSO), gamma-butyrolacton or its mixture.
According in even another embodiment of the inventive method, the solvent in polymer solution, hole liquid and precipitating bath is selected from 1-METHYLPYRROLIDONE, N-ethyl pyrrolidone, NOP or its mixture, preferred 1-METHYLPYRROLIDONE.
According in another embodiment of the inventive method, polymer solution comprises 17 ~ 18 % by weight polysulfones (PSU), polyether sulfone (PES) or poly arylene ether sulfone (PAES), 8 ~ 11.25 % by weight PVPs (PVP) and 70 ~ 75 % by weight solvents.
According in another embodiment of the inventive method, PVP (PVP) in polymer solution comprises the blend of at least two kinds of PVPs (PVP) homopolymers, wherein a kind of homopolymers has 10, 000g/mol ~ 100, 000g/mol, preferably 30, 000g/mol ~ 60, the average relative molecular mass (=low-molecular-weight PVP) of 000g/mol, another kind of homopolymers has 500, 000g/mol ~ 2, 000, 000g/mol, preferably 800, 000g/mol ~ 2, 000, the average relative molecular mass (=HMW PVP) of 000g/mol.
According in another embodiment of the inventive method, based on the gross weight of polymer solution, polymer solution comprise 1 ~ 10 % by weight, preferably 5 ~ 8 % by weight low-molecular-weight PVP and 1 ~ 5 % by weight, preferably 3 ~ 3.25 % by weight HMW PVP.According in even another embodiment of the inventive method, precipitating bath has the temperature of 22 ~ 27 DEG C.
According in another embodiment of the inventive method, hollow fiber spinning nozzle remains on 40 ~ 70 DEG C, the preferred temperature of 54 ~ 60 DEG C.
According in a kind of embodiment of the inventive method, the distance between the exhaust outlet of hollow fiber spinning nozzle and precipitating bath surface is 0 ~ 4cm.Exhaust outlet and polymer solution leave the outlet of spinning-nozzle.
According in another embodiment of the inventive method, the spinning speed of hollow-fibre membrane is 5 ~ 70 ms/min, preferably 7.5 ~ 45 ms/min.
According in another embodiment of the inventive method, polymer solution has and is at room temperature measured as 10000 ~ 100000mPa × s, the viscosity of preferably 21500 ~ 77000mPa × s.
The invention still further relates to according to hollow-fibre membrane that is above-mentioned or that obtain according to said method in haemodialysis as the sensing membrane (sensormembrane) of direct contacting blood, as sensing membrane and the transport membrane in bioprocess technology (deliverymembrane) in water application is as wastewater application.
There are at least 3 kinds of potential application in such film.Dive in the application all, the outside of this film and the potential fluid contact that can pollute this film.But, if not this situation, then may there is other application.
Product film, such as, have selective layer in inner side and have the hole of micrometer range in outside, if blood contacts with outer wall surface and can block or cause haemolysis in based on the application of blood.Below in application, the film described in present patent application shows obvious advantage.
Film according to the present invention is used as hemodialysis membrane when blood and this film contact outside.For this application, the outside of this film should have the hole dimension identical with commodity dialysis membrane (having blood contacting surfaces inside this dialysis membrane), diffusion coefficient, material form and roughness.According to hole dimension, cross-film is transmitted dynamics and may be controlled by diffusion.If hole dimension increases and keeps low roughness, then this transmission dynamics is based on diffusion and the combination of convection current.Require that the smooth outer surface of this film does not allow haemocyte and high molecular weight protein to enter this porous membrane structure.If haemocyte and high molecular weight protein enter this porous membrane structure, then this causes forming protein layer in blood cell breakage and structure.These two kinds of effects are not acceptable in this application.
The sensing membrane (microdialysis) of direct blood application can also be used as according to film of the present invention.If carry out the microdialysis in direct blood application, then fouling membrane is serious problem.If bore dia exceedes several microns, then cell can enter the outside of film.Meanwhile, high molecular weight protein can enter the loose structure of this film.This causing hole blocks and forms protein layer in the porous membrane structure inside of wall.In extreme circumstances, the outer surface of film can cause grumeleuse to be formed.Therefore the surface that high biological is compatible is required for such application.This is meaningful equally for the application as dialysis membrane.
The sensing membrane in the application of (giving up) water can also be used as according to film of the present invention.In such applications, ion concentration is importantly analyzed to control the ion concentration in waste water composition or analysis water-like product.To simplify the analysis, should only ion by film, and high molecular weight material not by.For this application, transmission should mainly based on diffusion.A large amount of convection current is transmitted can dilution analysis system.Ion transport should be stablized within some skies, some weeks or some moons simultaneously.Therefore the outside of this film should have low polluting property.This is again realized by the combination of material character, hole dimension and surface roughness.
The transport membrane in bioprocess technology can also be used as according to film of the present invention.May must control to add the fluid in technique or amount of substance in time in fermentation system.For allowing this material to dilute very equably, use the hollow-fibre membrane be suspended in stirred-tank reactor with smooth outer surface and special scattering nature.
Certainly this is only may apply according to some of film of the present invention.Other application that also can be benefited from such special film a large amount of may be there is.Generally speaking, can be summarized as follows according to the advantage of film of the present invention and character:
Outside-film, there is the narrowest hole dimension
-outside has smooth surface
-external structure has low protein adsorption character
-external structure has the compatible surface of high biological (namely low blood coagulation activity)
-there is 1*10 -4~ 100*10 -4cm 3/ (cm 2bar second) hydraulic diffusibility
-hydrophilic-spontaneous wetting film
-spongelike structure
The interior diameter of-50 ~ 2000 μm
The wall thickness of-10 ~ 200 μm
-based on diffusion or based on diffusion and the transmission of convection current
-mechanical stability
-allow the thin selective layer of high mass transfer rate.
For allowing the epidermis being prepared film outside by (DIPS) process that is separated of diffusion induction, many standards must be met.
By the loose structure on the direction of inner chamber after " selective " outer surface, there is the comparatively macropore up to several microns.This loose structure is obtained by phase separation process slowly.For allowing phase separation process slowly, the amount of solvent (solvent for polymer) is sufficiently high.But, hole liquid (also referred to as core flow, it be introduce in precipitation process doughnut hole or in the heart) and the solvent of precipitating bath middle and high concentration cause fiber unstable.This makes to enter precipitating bath and leave precipitating bath to be all difficult to obtain stable fiber.The solvent strength that problem is to regulate by this way in precipitation process (center and precipitating bath in) and precipitating bath temperature, namely it allows to be formed and outer surface has hole little on specific inner surface and the film with the unusual light outer surface for good biocompatibility.
Problem be to find a kind of like this prepare window, it allows the enough high concentrations regulating solvent in the heart in (i), to form the very open architecture allowed by the little resistance to mass tranfer of film, (ii) solvent strength in precipitating bath, to obtain the smooth surface structure outside film, it has 1 ~ 10nm at selective layer and has the hole of high biological biocompatible surface (material composition, roughness etc.), and the spinning condition that (iii) is stable.The main technologic parameters of spinning-drawing machine is as follows:
Polymer composition in-polymer solution
The temperature of-spinning-nozzle
The design of-spinning-nozzle
Distance between-spinning-nozzle and precipitating bath
The condition of the atmosphere between-spinning-nozzle and precipitating bath
The size of-doughnut
The composition of-hole liquid
The composition of-precipitating bath
The temperature of-precipitating bath
-spinning speed
-fiber by precipitating bath time/distance.
Described parameter is also imperfect.This is only the expression providing relevant technological parameters and complexity.
When obtained polymer solution, for this formation see such as embodiment 1, this polymer solution pumping is formed liquid hollow fiber by spinning-nozzle.This solvent strength in the liquid of hole causes the open architecture inside film.Distance between spinning-nozzle and precipitating bath, the solvent strength scope in precipitating bath and fiber cause the surface texture of unusual light on outer surface by time of precipitating bath and distance.According in a kind of embodiment of the inventive method, the time in precipitating bath is 2 ~ 60 seconds.
Minimum hole is in the outside of film.Hole inside film and overall structure much bigger.The selective layer in outside is used for direct contacting blood.Problem is to regulate spinning condition to meet the structure distribution of film, i.e. biocompatibility, little resistance to mass tranfer etc.
Solvent strength in precipitating bath and temperature interact each other strongly.Allow solvent strength to decline when temperature raises, obtain identical structural form, hole dimension and hydraulic diffusibility.But, technology restriction is there is when raising the temperature of precipitating bath.
Based on the outer field form of this special film and characteristic and normal dialysis film selective layer (inner side) can ratio characteristic, confirm that the biocompatibility of this film is very good.But, in order to strengthen this point even further, by valuable for functionalized for the outer surface of this film possibility.A kind of selection is that heparin covalent is bonded to this surface.For allowing covalent bonding heparin, can as use plasma igniting disclosed in WO2006/006918 or WO03/090910 and this film of precursor gases process containing functional group.
Accompanying drawing explanation
Fig. 1 a ~ 1d shows the hollow-fibre membrane obtained by embodiment 1 below according to one embodiment of this invention.
Fig. 2 a ~ 2d shows the hollow-fibre membrane obtained by embodiment 2 below according to another embodiment of the invention.
Fig. 3 a ~ 3d shows the hollow-fibre membrane obtained by embodiment 3 below according to another embodiment of the invention.
Fig. 4 a ~ 4d shows the hollow-fibre membrane obtained by embodiment 4 below according to another embodiment of the invention.
Fig. 5 a ~ 5d shows the hollow-fibre membrane obtained by embodiment 5 below according to another embodiment of the invention.
Fig. 6 a ~ 6d shows the hollow-fibre membrane comparative example that the face comparative example of pressing obtains.
materials and methods
AFM analyzes:
Use the AFM of DigitalInstruments/Veeco, model NanoScopeIIIaMultiMode carries out AFM research.For making the interaction between measuring probe and membrane material/film surface reach minimum, TappingMode is adopted to obtain data.These can the stabilized image/data of surface topography of produced film outer surface.Due to the aperture of this doughnut film outer surface and the surface of unusual light, use the special probe that probe pinpoint radius is little.Measuring probe point (Nanosensors, model SSS-NCH (SuperSharpSilicon)) used in the application has the typical tip angle (tipangle) of R ≈ 2nm.NCH (Nanosensors) point with the typical tip angle of R ≈ 10nm is used to measure the slightly high sample of some surface roughnesses.Measured sample size is 2 × 2 μm or 5 × 5 μm.
For measuring, with two-sided tape, this membrane sample is placed on flat substrate.AFM (AFM) is adopted to characterize the surface area of 5 × 5 μm, 2 × 2 μm and 1 × 1 μm.Each data group of different images shown in analyzing, utilizes the roughness parameter (Ra, Rq) that formulae discovery is below different:
R q = 1 N Σ i = 1 N Z i 2
R a = 1 N Σ i = 1 N | Z i |
N=data point sum
Z idata point height more than=the average image plane
Prepared by film bundle:
Bundle (handbundle) preparation
In order to prepare fibre bundle with the suitable method successfully carrying out testing, be necessary after spinning technique, prepare film bundle.First processing step is specific length fibre bundle being cut into 23cm.Next processing step forms by sealing fiber end.Optics controls to guarantee that all fibres end all seals.Then in the end-transfer of fibre bundle being covered to potting (potting).Potting lid machinery is fixing, and potting pipe is placed in potting covers.Subsequently, potting is completed with polyurethane.After potting, must guarantee that polyurethane can solidify at least one sky.In a next process step, the film bundle through potting is cut into specific length.Last processing step is that optics controls fibre bundle.In this processing step process, control point below:
-kerf quality (whether otch is smooth or whether there is any knife wound);
-potting quality (quantity of the spinning process split shed fiber that fiber potting reduces, or whether there is any visible vacancy not having polyurethane).
After optics controls, by film Shu Cunfang to dry, then they are used for different performance tests.The preparation of little module:
Little module [fibre bundle namely in housing] is prepared by associated process steps.Little module must guarantee that fiber obtains protecting and very clean preparation method, because biocompatibility test human plasma carries out.The preparation difference of little module is:
-fibre bundle is cut into the specific length of 20cm;
-before sealing fiber end, fibre bundle is transferred in housing; And
-little module being placed in hollow drying oven before potting spends the night.
The preparation of filter:
It is 0.5 ~ 0.6m that this filter (i.e. dialyzer) has effective surface area 2about 8000 ~ 10000 fibers.The feature of filter is that cylindrical shell has two connectors for dialysis fluid, and housing two ends have the lid of applying, and each have a blood connector placed in the middle.Key step below preparation technology's (after winding) can be divided into:
-by be cut into (20cm long) bundle transfer to there are special bundle pincers housing in;
The two ends of-sealed beam;
-use polyurethane (PUR) by fiber potting in housing;
-cutting tip, to make fiber open, wherein requires smooth surface;
-naked eyes control the defect in the sealing end of fiber or PUR block; And
-will cover and glue together with blood connector.
Bundle and the hydraulic diffusibility (Lp) of little module:
In (bundle) to
By under stress the hydraulic pressure of exact definition volume being crossed film bundle (side seal of film bundle) and time needed for measuring measures the hydraulic diffusibility of this film bundle.Hydraulic diffusibility can be calculated by measured time, film effective surface area, institute's applied pressure and the water volume pressing through this film.Film effective surface area can be calculated by fiber number, fibre length and fiber interior diameter.Film bundle must be soaked 30 minutes before carrying out by test.Therefore, film bundle is put in the box that 500ml ultra-pure water is housed.After 30 minutes, film bundle is transferred in test macro.The equipment that this test macro mechanically can be realized at this by water-bath and the film bundle of temperature 37 DEG C forms.The fill level of water-bath must guarantee film bundle in designated equipment below water surface.For the test result avoiding film seepage to make the mistake, the integrity test of film bundle and this test macro must be carried out in advance.This integrity test is undertaken by film bundle air being pressed through one end sealing.Bubble shows that film bundle or testing equipment have leakage.Must check that this leakage is relevant with the wrong implementation of film bundle in testing equipment, still really there is film seepage.If film seepage detected, then must abandon this film bundle.Integrity test institute applied pressure must have at least identical value with institute's applied pressure in the mensuration process of hydraulic diffusibility, with to guarantee in the measuring process of hydraulic diffusibility can not because of applying hypertonia and revealing.From (little module) in:
Carry out this measurement according to identical measuring principle in above-mentioned measurement from inside to outside.
The hydraulic diffusibility (Lp) of filter:
From inside to outside:
From different for the test program restrainted, by making the water of exact definition volume flow through film, and measuring transmembrane pressure, measuring the hydraulic diffusibility of filter.Before the start of the measurement, filter (film inside and the room between housing and film) must be full of test fluid flow completely.Thus by beaing removing air gently.By test fluid flow, there is the pure water that concentration is the sodium chloride of 0.9%, be located at the temperature of 38 DEG C, and be pumped into the blood inlet of filter thus, close exit blood connector and the entrance be connected of dialysing at this.Measurement carries out 5 minutes, and the mean value of calculating pressure.The calculating of hydraulic diffusibility with for restrainting/description of little module is identical.
From outside to inside:
Measuring principle with measure from inside to outside identical, difference is reverse filtration pure water.At this, pump fluid into dislysate import, and blood inlet and dislysate outlet are all closed.
Permeability test/diffusion experiment bundle:
Diffusion experiment is carried out, to measure the scattering nature of film with the chloride solution identical with concentration and blood.Bundle will be put into measuring unit.This measuring unit allows the inside of doughnut to pass through chloride solution.In addition, test cell is full of water completely, and sets distilled water lateral flow to carry off from the chlorion of doughnut Inside To Outside by film cross section.Accurate adjustment pressure ratio, its target is zero filtration, and it makes the scattering nature by means of only reaching the combine measured film of muriatic Cmax gradient instead of diffusion and convection character between inside doughnut and around doughnut.Measure when starting and sample from pond, and got trapped substance sample after 10 minutes and 20 minutes.Then these samples of liquor argenti nitratis ophthalmicus titration are used, to measure chlorine ion concentration.According to the chlorine ion concentration of gained, the active surface sum flox condition of film, chloride permeability rate can be calculated.Can by the permeability of other material/protein of same device analysis.Test using urea as test substances.Adopt standard method by the urea concentration quantification in different solutions.EliasKlein etc. describe this and are used for measuring permeability (P m) method.
E.Klein，F.F.Holland，A.Donnaud，A.Lebeouf，K.Eberle，“Diffusiveandhydraulicpermeabilitiesofcommerciallyavailablehemodialysisfilmsandhollowfibers”，JournalofMembraneScience，2(1977)349-364。
E.Klein，F.F.Holland，A.Lebeouf，A.Donnaud，J.K.Smith，“Transportandmechanicalpropertiesofhemodialysishollowfibers”，JournalofMembraneScience，1(1976)371-396。
Other document: bibliography mentioned in E.Klein paper.
Effective diffusion cofficient (the D of predetermined substance (material, ion or protein) meff) with the membrane diffusion permeability (P of this material m) by D meff=P m× Δ z is associated, and wherein Δ z is diffusion length (wall thickness of film).
viscosity measurement:
About polymer solution of the present invention, term " viscosity " refers to kinematic viscosity, except as otherwise noted.The unit of the kinematic viscosity of this polymer solution provides by centipoise (cp) or mPa × s.For measuring the viscosity of polymer solution, use the commodity flow graph (SR2000) of RhemoeticScientificLtd..Polymer solution is placed between two temperature control plates.Measure and carry out at 22 DEG C.Other measuring conditions all are all according to the instruction of manufacturer.
embodiment
Embodiment 1
By by polyether sulfone (BASFUltrason6020) and PVP (PVP; BASFK30 and K85) be dissolved in 1-METHYLPYRROLIDONE (NMP), obtained polymer solution.In polymer spinning solution, this weight fraction of these different components is: PES-PVPK85-PVPK30-NMP:18-3.25-8-70.75.The viscosity of this polymer solution is 53560mPa × s.
For preparing this solution, first NMP being loaded middle port and being furnished with in the there-necked flask of finger-type dasher.In NMP, add PVP, and stir at 50 DEG C, until obtained uniform clear solution.Finally, polyether sulfone (PES) is added.Mixture is stirred at 50 DEG C, until obtain limpid full-bodied solution.This hot solution is cooled to 20 DEG C and degassed.For making solution completely degassed, this full-bodied polymer solution is transferred in stable rustless steel container.Subsequently this container tightly to be sealed and to its application of vacuum.By this solution under 50mmHg degassed 6 hours.In this degasification process, rotary container to form larger surface and polymer solution that more film is thick in a reservoir, thus improves degasification process.
By polymer solution is heated to 50 DEG C, and it is made to form film by spinning-nozzle (also referred to as spinning die head or spinning head).Use water and containing the mixture of 42 % by weight water and 58 % by weight NMP as hole liquid.The temperature of spinning-nozzle is 55 DEG C.Hollow-fibre membrane is formed under the spinning speed of 10 ms/min.The liquid capillary thing leaving spinning-nozzle is sent in the NMP/ water-bath (NMP concentration is 52%) of temperature 26 DEG C.The length of the distance between spinning-nozzle outlet and precipitating bath is 4cm.Formed hollow-fibre membrane is guided through the water-bath of temperature 65 DEG C.The interior diameter of wet hollow-fibre membrane is 1012 μm, and overall diameter is 1152 μm, and has complete anisotropic membrane structure.The active separating layer of this film is in outer wall surface.Active separating layer is defined as the layer with minimum aperture.Adopt preceding method, the intrafascicular hydraulic diffusibility (Lp value) measuring this film from inside to outside.This film shows 3.5 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 1 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 1 b shows the close-up view in hollow fiber walls cross section, and this figure shows that this wall has unsymmetric structure and general structure is spongelike structure.The layer that in this hollow fiber walls, existence 5 is different, and these different layers mark; Layers different as seen from Fig. has different hole dimensions and different mass densityes.Ground floor is outer selective layer, and this layer has minimum hole and the highest mass density.The second layer has the hole larger than ground floor and low mass density.Third layer has the hole less than the second layer and high mass density, and the hole larger than ground floor and low mass density.4th layer has the hole larger than ground floor, the second layer and third layer and low mass density.Layer 5 has than the 4th layer of little hole and high mass density.Fig. 1 c shows inner wall surface, and Fig. 1 d shows outer wall surface, and outer wall surface unusual light and there is smooth hole.
By above disclosed with have R ≈ 2nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 4.9nm, R qfor 6.3nm; For the sample of size 5 × 5 μm, roughness parameter R afor 7.9nm, R qfor 10.0nm.
Embodiment 2
Embodiment 2 is carried out to the polymer solution of same composition in such as embodiment 1.The viscosity of polymer solution is 60200mPa × s.
Keep polymer preparation procedure as described in Example 1.Film forms change of program these points:
The temperature of-spinning-nozzle: 54 DEG C
-spinning speed: 7.5 ms/min
Distance between-spinning-nozzle and precipitating bath: 2.5cm
The temperature of-precipitating bath: 27 DEG C
Other processing step keeps by the carrying out in embodiment 1.The interior diameter of wet hollow-fibre membrane is 1464 μm, and overall diameter is 1592 μm, and has complete anisotropic membrane structure.The active separating layer of this film is in outer wall surface.Active separating layer is defined as the layer with minimum aperture.Adopt preceding method, the intrafascicular hydraulic diffusibility (Lp value) measuring this film from inside to outside.This film shows 3.4 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 2 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 2 b shows the close-up view in hollow fiber walls cross section, and this figure shows that this wall has unsymmetric structure and general structure is spongelike structure.The layer that in this hollow fiber walls, existence 5 is different, and these different layers mark; Layers different as seen from Fig. has different hole dimensions and different mass densityes.Ground floor is outer selective layer, and this layer has minimum hole and the highest mass density.The second layer has the hole larger than ground floor and low mass density.Third layer has the hole less than the second layer and high mass density, but has the hole larger than ground floor and low mass density.4th layer has the hole larger than ground floor, the second layer and third layer and low mass density.Layer 5 has than the 4th layer of little hole and high mass density.Fig. 2 c shows inner wall surface, and Fig. 2 d shows outer wall surface, and outer wall surface unusual light and there is smooth hole.
By above disclosed with have R ≈ 2nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 1.9nm, R qfor 2.4nm; For the sample of size 5 × 5 μm, roughness parameter R afor 2.8nm, R qfor 3.6nm.
Embodiment 3
Embodiment 3 is carried out to the polymer solution of same composition in such as embodiment 1.The viscosity of polymer solution is 59300mPa × s.
Keep polymer preparation procedure as described in Example 1.Film forms change of program these points:
-hole liquid (H 2: 38 % by weight: 62 % by weight O: NMP)
The concentration of NMP in-precipitating bath: 64 % by weight
Distance between-spinning-nozzle and precipitating bath: 3cm
The temperature of-precipitating bath: 22 DEG C
Other processing step keeps by the carrying out in embodiment 1.Unique difference is that fiber is of different sizes.The interior diameter of this hollow-fibre membrane is 203 μm, and overall diameter is 281 μm, and has complete anisotropic membrane structure.The active separating layer of this film is in outer wall surface.Active separating layer is defined as the layer with minimum aperture.Adopt preceding method, from inside to outside intrafascicular and measure the hydraulic diffusibility (Lp value) of this film from outside to inside in little module.When measuring from inside to outside, this film shows 6.7 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility; When measuring from outside to inside, this film shows 6.7 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 3 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 3 b shows the close-up view in hollow fiber walls cross section, and this figure shows that this wall has unsymmetric structure and general structure is spongelike structure.The layer that in this hollow fiber walls, existence 4 is different, and these different layers mark; Layers different as seen from Fig. has different hole dimensions and different mass densityes.Ground floor is outer selective layer, and this layer has minimum hole and the highest mass density.The second layer has the hole larger than ground floor and low mass density.Third layer has the hole less than the second layer and high mass density, but has the hole larger than ground floor and low mass density.4th layer has the hole larger than ground floor, the second layer and third layer and low mass density.Fig. 3 c shows inner wall surface, and Fig. 3 d shows outer wall surface, and outer wall surface unusual light and there is smooth hole.
By above disclosed with have R ≈ 2nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 3.3nm, R qfor 4.2nm; For the sample of size 5 × 5 μm, roughness parameter R afor 4.6nm, R qfor 5.7nm.
Embodiment 4
Embodiment 4 is carried out to the polymer solution of same composition in such as embodiment 1.The viscosity of polymer solution is 62100mPa × s.
Keep polymer preparation procedure as described in Example 1.Film forms change of program these points:
-hole liquid (H 2: 38 % by weight: 62 % by weight O: NMP)
The concentration of NMP in-precipitating bath: 69 % by weight
Other processing step keeps by the carrying out in embodiment 1.Unique difference is that fiber is of different sizes.The interior diameter of hollow-fibre membrane is 311 μm, and overall diameter is 395 μm, and has complete anisotropic membrane structure.The active separating layer of this film is in outer wall surface.Active separating layer is defined as the layer with minimum aperture.Adopt preceding method, the intrafascicular hydraulic diffusibility (Lp value) measuring this film from inside to outside.This film shows 27.0 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 4 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 4 b shows the close-up view in hollow fiber walls cross section, and this figure shows that this wall has unsymmetric structure and general structure is spongelike structure.The layer that in this hollow fiber walls, existence 5 is different, and these different layers mark; Layers different as seen from Fig. has different hole dimensions and different mass densityes.Ground floor is outer selective layer, and this layer has minimum hole and the highest mass density.The second layer has the hole larger than ground floor and low mass density.Third layer has the hole less than the second layer and high mass density, but has the hole larger than ground floor and low mass density.4th layer has the hole larger than ground floor, the second layer and third layer and low mass density.Layer 5 has than the 4th layer of little hole and high mass density.Fig. 4 c shows inner wall surface, and Fig. 4 d shows outer wall surface, and outer wall surface unusual light and there is smooth hole.
By above disclosed with have R ≈ 2nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 4.6nm, R qfor 5.9nm; For the sample of size 5 × 5 μm, roughness parameter R afor 7.2nm, R qfor 9.1nm.
Embodiment 5
Keep polymer preparation procedure as described in example 1 above.The viscosity of polymer solution is 53560mPa × s.Film forms change of program these points:
-hole liquid (H 2: 34 % by weight: 66 % by weight O: NMP)
The temperature of-spinning-nozzle: 60 DEG C
-spinning speed: 45 ms/min
Distance between-spinning-nozzle and precipitating bath: 0cm
The concentration of NMP in-precipitating bath: 62 % by weight
The temperature of-precipitating bath: 25 DEG C
Other processing step keeps by the carrying out in embodiment 1.The interior diameter of this hollow-fibre membrane is 117 μm, and overall diameter is 163 μm, and has complete anisotropic membrane structure.The active separating layer of this film is in outside.Active separating layer is defined as the layer with minimum aperture.Adopt preceding method, measure the hydraulic diffusibility (Lp value) of this film in the filter from inside to outside.This film shows 13.6 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 5 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 5 b shows the close-up view in hollow fiber walls cross section, and this figure shows that this wall has unsymmetric structure and general structure is spongelike structure.The layer that in this hollow fiber walls, existence 4 is different, and these different layers mark; Layers different as seen from Fig. has different hole dimensions and different mass densityes.Ground floor is outer selective layer, and this layer has minimum hole and the highest mass density.The second layer has the hole larger than ground floor and low mass density.Third layer has the hole less than the second layer and high mass density, but has the hole larger than ground floor and low mass density.4th layer has the hole larger than ground floor, the second layer and third layer and low mass density.Fig. 5 c shows inner wall surface, and Fig. 5 d shows outer wall surface, and outer wall surface unusual light and there is smooth hole.
By above disclosed with have R ≈ 10nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 6.8nm, R qfor 8.4nm; For the sample of size 5 × 5 μm, roughness parameter R afor 7.3nm, R qfor 9.4nm.Comparative example
First experiment is carried out to the polymer solution of same composition in such as embodiment 1.The viscosity of polymer solution is 62100mPa × s.
Keep polymer preparation procedure as described in Example 1.Film forms change of program these points:
-hole liquid (H 2: 38 % by weight: 62 % by weight O: NMP)
The concentration of NMP in-precipitating bath: 72 % by weight
Other processing step keeps by the carrying out in embodiment 1.Unique difference is that fiber is of different sizes.The interior diameter of hollow-fibre membrane is 312 μm, and overall diameter is 396 μm, and has complete anisotropic membrane structure.Adopt preceding method, the intrafascicular hydraulic diffusibility (Lp value) measuring this film from inside to outside.This film shows 120 × 10 -4cm 3/ (cm 2bar second) hydraulic diffusibility.
Fig. 6 a shows the scanning electron microscopy in hollow-fibre membrane cross section.Fig. 6 b shows the close-up view in hollow fiber walls cross section.Fig. 6 c shows inner wall surface, and Fig. 6 d shows outer wall surface.From Fig. 6 c and Fig. 6 d, outer wall surface shows the hole larger than inner wall surface.In addition, the smoothness of outer wall surface declines also more coarse.
By above disclosed with have R ≈ 10nm typical tip angle probe measurement and calculate the roughness of outer wall surface.For the sample of size 2 × 2 μm, roughness parameter R afor 19.8nm, R qfor 26.4nm; For the sample of size 5 × 5 μm, roughness parameter R afor 23.3nm, R qfor 30.5nm, this is obviously beyond the scope of the invention.
Should be understood that the variations and modifications of embodiment described herein will be apparent to those skilled in the art.This change and amendment can be carried out when not departing from the spirit and scope of the present invention and do not reduce adjoint advantage.Therefore this change and amendment to be intended to contain by claims.

Claims (6)

1. a micro-dialysis device, it comprises the sensing membrane applied for direct blood, described sensing membrane is such semipermeable hallow fibre film, its inner chamber that there is outer wall surface, inner wall surface and extend along its length, and have selective layer in outer wall surface, the feature of described film is to have minimum hole dimension in outer wall surface, and its outer wall surface at nanoscale Smooth, continuously and evenly, substantially roughness is not had, roughness parameter R aand R qbe not more than 10nm, described roughness utilizes AFM (AFM) to measure, and utilizes equation below to calculate roughness parameter R aand R q:
R a = 1 N Σ i = 1 N | Z i | R q = 1 N Σ i = 1 N Z i 2
Wherein N is data point sum, Z ithe height of data point more than the average image plane, membranous wall wherein between outer wall surface from inner wall surface has hole dimension at least 4 layer different with mass density, and wherein from outer wall surface, the third layer of calculating has the hole dimension of 2 layers little than direct contiguous described layer both sides and high mass density.
2. the device of claim 1, the membranous wall wherein between outer wall surface from inner wall surface has hole dimension 4 layer different with mass density; Ground floor, in outer wall surface, has minimum hole dimension and the highest mass density; The second layer adjoins ground floor and has the hole dimension larger than ground floor and low mass density; Third layer adjoins the second layer and has the hole dimension less than the second layer and high mass density, but has the hole dimension larger than ground floor and low mass density; 4th layer, in inner wall surface also adjacent third layer, has the hole dimension larger than ground floor, the second layer and third layer and low mass density.
3. the device of claim 2, wherein said film has layer 5 in addition, and it is in inner wall surface, adjoins the 4th layer and has than ground floor, the second layer, third layer and the 4th layer of large hole dimension and low mass density.
4. the device of claim 2, wherein said film has layer 5 in addition, and it is in inner wall surface, adjoins the 4th layer and has than the 4th layer of little hole dimension and high mass density.
5. the device any one of aforementioned claim, wherein said film comprises containing polysulfones PSU, polyether sulfone PES or poly arylene ether sulfone PAES; With the polymer composition of PVP PVP.
6. the device of claim 5, PVP PVP in wherein said film comprises the blend of at least two kinds of PVP PVP homopolymers, wherein a kind of homopolymers has 10,000g/mol ~ 100, the average relative molecular mass of 000g/mol, another kind of homopolymers has 500,000g/mol ~ 2, the average relative molecular mass of 000,000g/mol.
CN201210014783.XA 2006-10-18 2007-10-11 Micro-dialysis device Active CN102553441B (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US82996506P 2006-10-18 2006-10-18
SE0602189 2006-10-18
US60/829,965 2006-10-18
SE0602189-3 2006-10-18
CN2007800391319A CN101578129B (en) 2006-10-18 2007-10-11 Hollow fiber membrane and method for manufacturing thereof

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN2007800391319A Division CN101578129B (en) 2006-10-18 2007-10-11 Hollow fiber membrane and method for manufacturing thereof

Publications (2)

Publication Number Publication Date
CN102553441A CN102553441A (en) 2012-07-11
CN102553441B true CN102553441B (en) 2016-04-13

Family

ID=41272772

Family Applications (2)

Application Number Title Priority Date Filing Date
CN2007800391319A Active CN101578129B (en) 2006-10-18 2007-10-11 Hollow fiber membrane and method for manufacturing thereof
CN201210014783.XA Active CN102553441B (en) 2006-10-18 2007-10-11 Micro-dialysis device

Family Applications Before (1)

Application Number Title Priority Date Filing Date
CN2007800391319A Active CN101578129B (en) 2006-10-18 2007-10-11 Hollow fiber membrane and method for manufacturing thereof

Country Status (11)

Country Link
US (3) US8596467B2 (en)
EP (3) EP2383031B1 (en)
JP (1) JP5113178B2 (en)
KR (1) KR101413935B1 (en)
CN (2) CN101578129B (en)
AT (1) ATE487533T1 (en)
AU (1) AU2007312413B2 (en)
CA (1) CA2660161C (en)
DE (1) DE602007010505D1 (en)
DK (1) DK2083939T3 (en)
WO (1) WO2008046779A1 (en)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8535537B2 (en) 2006-10-19 2013-09-17 Joanneum Research Forschungsgesellschaft Mbh Devices for and methods of monitoring a parameter of a fluidic sample by microdialysis
EP2168666A1 (en) 2008-09-25 2010-03-31 Gambro Lundia AB Irradiated membrane for cell expansion
EP2314672B1 (en) 2008-09-25 2015-04-15 Gambro Lundia AB Hybrid bioartificial kidney
EP2168668A1 (en) 2008-09-25 2010-03-31 Gambro Lundia AB Membrane for cell expansion
EP2177603A1 (en) 2008-09-25 2010-04-21 Gambro Lundia AB Device for renal cell expansion
US9795932B2 (en) * 2008-12-25 2017-10-24 Toyo Boseki Kabushiki Kaisha Porous hollow fiber membrane and a porous hollow fiber membrane for the treatment of a protein-containing liquid
JP2011024708A (en) * 2009-07-23 2011-02-10 Toyobo Co Ltd Hollow fiber membrane for blood purification which is excellent in workability for module assembly, and method for manufacturing the same
EP2501286A4 (en) * 2009-11-16 2013-09-04 Maquet Critical Care Ab Self-flowing measuring system
JP5445195B2 (en) * 2010-02-10 2014-03-19 東洋紡株式会社 Blood purifier
CN103237763B (en) * 2011-01-20 2015-10-21 英派尔科技开发有限公司 The method of adsorbent composition and the described adsorbent composition of use
DE102011015077A1 (en) * 2011-03-24 2012-09-27 MAHLE InnoWa GmbH Device for producing a membrane
EP2556848A1 (en) 2011-08-08 2013-02-13 Gambro Lundia AB Separation material comprising saccharide ligands
EP2556849A1 (en) 2011-08-08 2013-02-13 Gambro Lundia AB Separation material
EP2567750B1 (en) 2011-09-08 2014-12-24 Gambro Lundia AB Hollow fiber membrane
US9044712B2 (en) 2011-09-12 2015-06-02 Idex Health & Science, Llc Supersaturated fluid degassing
FR2985438A1 (en) * 2012-01-10 2013-07-12 Alstom Technology Ltd MEMBRANE FOR GASEOUS EFFLUENT FILTRATION PROCESS OF INDUSTRIAL INSTALLATION
FR2985595A1 (en) 2012-01-10 2013-07-12 Alstom Technology Ltd PROCESS FOR FILTRATION OF HARMFUL GASEOUS EFFLUENTS OF A NUCLEAR POWER PLANT
FR2985437A1 (en) 2012-01-10 2013-07-12 Alstom Technology Ltd PROCESS FOR FILTRATION OF GASEOUS EFFLUENTS OF AN INDUSTRIAL PLANT
BR112014012145B1 (en) * 2012-01-25 2021-03-16 Fresenius Hemocare Italia Srl blood filter, blood processing system and use of a filter
US9005496B2 (en) * 2012-02-01 2015-04-14 Pall Corporation Asymmetric membranes
EP2636442A1 (en) * 2012-03-05 2013-09-11 Gambro Lundia AB Low cut-off ultrafiltration membranes
WO2013171280A1 (en) * 2012-05-15 2013-11-21 Solvay Specialty Polymers Usa, Llc High performance polysulfones made from cycloaliphatic diols
ES2626754T3 (en) 2012-11-26 2017-07-25 Gambro Lundia Ab Adsorption device that combines beads and hollow fiber membranes
CN103882536B (en) * 2012-12-19 2016-12-28 财团法人工业技术研究院 Hollow fiber for adsorption or filtration and method for producing the same
US9222200B2 (en) 2012-12-19 2015-12-29 Industrial Technology Research Institute Spinning device
EP3424577A3 (en) * 2013-03-15 2019-02-20 Bio-rad Laboratories, Inc. Degassing of a liquid to controlled level in composite tube
EP2845641B1 (en) 2013-09-05 2018-05-09 Gambro Lundia AB Permselective asymmetric membranes with high molecular weight polyvinylpyrrolidone, the preparation and use thereof
DE102013015876B4 (en) * 2013-09-23 2019-11-07 Fresenius Medical Care Deutschland Gmbh fuel cell
KR102140264B1 (en) 2013-12-20 2020-07-31 주식회사 엘지화학 Hollow fiber membrane
JP6598082B2 (en) * 2014-01-21 2019-10-30 ネフロ−ソリューションズ アーゲー Dialysis machine with dialyzer
EP4335539A3 (en) * 2014-03-29 2024-05-01 Princeton Trade and Technology Inc. Blood processing cartridges and systems, and methods for extracorporeal blood therapies
CN105310141B (en) * 2014-05-29 2018-07-24 曹义鸣 Two points five highly-breathable masks of anti-PM, mask or mask
CN104155227A (en) * 2014-07-28 2014-11-19 重庆大学 Oil-gas permeability testing apparatus based on hollow fibrous membrane and oil-gas permeability testing method
US10426884B2 (en) 2015-06-26 2019-10-01 Novaflux Inc. Cartridges and systems for outside-in flow in membrane-based therapies
US10399040B2 (en) 2015-09-24 2019-09-03 Novaflux Inc. Cartridges and systems for membrane-based therapies
CN105233712A (en) * 2015-10-31 2016-01-13 宁波欧梵卫浴有限公司 Preparation method for water-purifying polyether sulfone hollow fiber membrane
EP3178539A1 (en) 2015-12-11 2017-06-14 Gambro Lundia AB Filter device, system and method for filtration of fluids
EP3195921A1 (en) * 2016-01-22 2017-07-26 Gambro Lundia AB Filter membrane and device
DE102016012722A1 (en) * 2016-10-24 2018-04-26 Fresenius Medical Care Deutschland Gmbh Method for determining a permeation property of hollow fiber membranes
RU2655140C1 (en) * 2017-02-02 2018-05-23 Публичное акционерное общество криогенного машиностроения (ПАО "Криогенмаш") Fiberglass composite gas-filling membrane and the method of its production
RU2659054C9 (en) * 2017-02-02 2019-03-19 Публичное акционерное общество криогенного машиностроения (ПАО "Криогенмаш") Composition of the spinning solution for formation of the hollow fiber gas separation membrane and method of production of the membrane
EP3415225B1 (en) 2017-06-14 2021-03-03 Gambro Lundia AB System and method for filtration and/or dilation of fluids
WO2019173752A1 (en) 2018-03-08 2019-09-12 Repligen Corporation Tangential flow depth filtration systems and methods of filtration using same
CN112165983A (en) * 2018-05-25 2021-01-01 瑞普利金公司 Tangential flow filtration systems and methods
EP3854430A4 (en) * 2018-09-20 2022-06-29 Daicen Membrane-Systems Ltd. Porous hollow fiber membrane
EP3903913A4 (en) * 2018-12-27 2022-05-04 Kolon Industries, Inc. Membrane humidifier for fuel cell, comprising multi-channel hollow fiber membranes
US20220267497A1 (en) 2019-08-06 2022-08-25 Solvay Specialty Polymers Usa, Llc Membrane and polymer for the manufacture thereof
JP2023529177A (en) 2020-06-04 2023-07-07 ノヴァフラックス・インコーポレイテッド Hollow fibers for outside-in dialysis applications
CN113117535A (en) * 2021-04-15 2021-07-16 上海工程技术大学 Preparation method of homogeneous continuous fiber reinforced hollow fiber membrane and hollow fiber membrane prepared by same
CN114452823A (en) * 2022-01-29 2022-05-10 杭州科百特过滤器材有限公司 Hollow fiber membrane module for biomacromolecule tangential flow filtration and application thereof
CN114635200B (en) * 2022-03-11 2023-12-22 宁德新能源科技有限公司 Tubular nanofiber material, negative electrode plate and lithium metal battery

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030141242A1 (en) * 2000-05-23 2003-07-31 Kurth Christopher J. Polysulfonamide matrices

Family Cites Families (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5440287A (en) * 1977-09-06 1979-03-29 Kuraray Co Ltd Ethylene-vinyl alcohol copolymer membrane of improved performance and preparation thereof
JPS54145379A (en) * 1978-05-02 1979-11-13 Asahi Chem Ind Co Ltd Aromatic polysulfone hollow fiber semipermeable membrane
DE2935097A1 (en) * 1978-09-07 1980-03-20 Kuraray Co AETHYLENE / VINYL ALCOHOL COPOLYMER MEMBRANE
JPS55148209A (en) * 1979-04-27 1980-11-18 Kuraray Co Ltd Hollow ethylene-vinyl alcohol membrane and its production
US4387024A (en) * 1979-12-13 1983-06-07 Toray Industries, Inc. High performance semipermeable composite membrane and process for producing the same
US4822489A (en) * 1981-08-22 1989-04-18 Asahi Kasei Kogyo Kabushiki Kaisha Aromatic polysulfone type resin hollow fiber membrane and a process for producing the same
DE3149976A1 (en) 1981-12-17 1983-06-30 Hoechst Ag, 6230 Frankfurt MACROPOROUS ASYMMETRIC HYDROPHILE MEMBRANE MADE OF SYNTHETIC POLYMER
EP0183757B1 (en) 1984-06-13 1991-10-30 Lyonnaise Des Eaux - Dumez Method of producing hollow fibres and their applications particularly in the field of membrane-type separations
DE3426331A1 (en) 1984-07-17 1986-01-30 6380 Bad Homburg Fresenius AG ASYMMETRIC MICROPOROUS HOLLOW FIBER FOR HAEMODIALYSIS AND METHOD FOR THE PRODUCTION THEREOF
JPS621404A (en) * 1985-06-27 1987-01-07 Mitsubishi Rayon Co Ltd Poly-composite hollow fiber membrane and its manufacturing process
SE460521B (en) * 1987-08-31 1989-10-23 Gambro Dialysatoren PERMSELECTIVE ASYMMETRIC MEMBRANE AND PROCEDURES FOR ITS PREPARATION
JPH0829242B2 (en) * 1988-07-12 1996-03-27 ダイセル化学工業株式会社 Polysulfone hollow fiber membrane
AU4529289A (en) * 1988-10-17 1990-05-14 Sepracor, Inc. Process for the covalent surface modification of hydrophobic polymers and articles made therefrom
JP2905208B2 (en) * 1988-12-20 1999-06-14 旭化成工業株式会社 Polysulfone hollow fiber separation membrane
US5762798A (en) * 1991-04-12 1998-06-09 Minntech Corporation Hollow fiber membranes and method of manufacture
US5340480A (en) 1992-04-29 1994-08-23 Kuraray Co., Ltd. Polysulfone-based hollow fiber membrane and process for manufacturing the same
CA2136006C (en) 1992-06-23 1999-11-30 Louis C. Cosentino Hollow fiber membrane incorporating a surfactant and process for preparing same
DK0703819T3 (en) * 1993-06-15 1998-06-02 Uop Inc Process for the preparation of gas separation composite membranes
US5702503A (en) * 1994-06-03 1997-12-30 Uop Composite gas separation membranes and making thereof
DE69527961T2 (en) * 1994-06-07 2003-04-10 Mitsubishi Rayon Co POROUS POLYSULPHONE MEMBRANE AND METHOD FOR THE PRODUCTION THEREOF
WO1996035504A1 (en) 1995-05-09 1996-11-14 Teijin Limited Hollow-fiber membrane of polysulfone polymer and process for the production thereof
JP3617194B2 (en) * 1995-06-30 2005-02-02 東レ株式会社 Permselective separation membrane and method for producing the same
US6355730B1 (en) * 1995-06-30 2002-03-12 Toray Industries, Inc. Permselective membranes and methods for their production
US5706806A (en) * 1996-04-26 1998-01-13 Bioanalytical Systems, Inc. Linear microdialysis probe with support fiber
JPH11541A (en) * 1997-06-12 1999-01-06 Mitsubishi Rayon Co Ltd Hollow fiber membrane and its production
US5914039A (en) * 1997-07-01 1999-06-22 Zenon Environmental Inc. Filtration membrane with calcined α-alumina particles therein
DE19817364C1 (en) 1998-04-18 1999-07-08 Fresenius Medical Care De Gmbh Hydrophilic asymmetric membrane used in ultrafiltration and reverse osmosis
DE19913416A1 (en) 1999-03-25 2000-10-05 Jostra Medizintechnik Ag Device with at least one membrane in the form of a hollow fiber for filtering liquids
AT408280B (en) * 1999-04-09 2001-10-25 Akg Acoustics Gmbh DEVICE AND METHOD FOR DETERMINING THE REMAINING TIME OF BATTERY-OPERATED DEVICES
US6802820B1 (en) * 2000-04-13 2004-10-12 Transvivo, Inc. Specialized hollow fiber membranes for in-vivo plasmapheresis and ultrafiltration
SE519630C2 (en) * 2001-08-30 2003-03-18 Gambro Lundia Ab Catheter and method of manufacture thereof
CA2480432A1 (en) * 2002-04-16 2003-10-30 Pall Corporation Hollow fibres
SE527054C2 (en) 2002-04-23 2005-12-13 Gambro Lundia Ab Process for preparing a regioselective membrane
AU2003230426A1 (en) 2002-05-17 2003-12-02 Para Limited Hollow fiber membrane having supporting material for reinforcement, preparation thereof and spinneret for preparing the same
AU2003281177A1 (en) * 2002-07-12 2004-02-02 Kuraray Co., Ltd. Porous membrane
AU2003261571A1 (en) * 2002-09-12 2004-04-30 Asahi Medical Co., Ltd. Plasma purification membrane and plasma purification system
SE0203855L (en) * 2002-12-20 2004-06-21 Gambro Lundia Ab Perm-selective membrane
JP3551971B1 (en) 2003-11-26 2004-08-11 東洋紡績株式会社 Polysulfone permselective hollow fiber membrane
JP2005224604A (en) * 2004-01-16 2005-08-25 Asahi Kasei Medical Co Ltd Hemocatharsis membrane and hemocatharsis apparatus using the same
SE0401834D0 (en) 2004-07-09 2004-07-09 Gambro Lundia Ab A continuous method for the production of a regioselective porous hollow fiber membrane

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030141242A1 (en) * 2000-05-23 2003-07-31 Kurth Christopher J. Polysulfonamide matrices

Also Published As

Publication number Publication date
CN101578129A (en) 2009-11-11
US20140001115A1 (en) 2014-01-02
JP2010506709A (en) 2010-03-04
AU2007312413A1 (en) 2008-04-24
CA2660161A1 (en) 2008-04-24
US9156005B2 (en) 2015-10-13
US20150273400A9 (en) 2015-10-01
ATE487533T1 (en) 2010-11-15
CA2660161C (en) 2015-12-22
KR101413935B1 (en) 2014-06-30
KR20090071549A (en) 2009-07-01
CN102553441A (en) 2012-07-11
AU2007312413B2 (en) 2011-09-29
JP5113178B2 (en) 2013-01-09
EP2383031B1 (en) 2016-05-25
US20110031184A1 (en) 2011-02-10
EP2383031A1 (en) 2011-11-02
EP2083939B1 (en) 2010-11-10
EP2083939A1 (en) 2009-08-05
US20160023169A1 (en) 2016-01-28
US8596467B2 (en) 2013-12-03
DK2083939T3 (en) 2011-02-14
AU2007312413A2 (en) 2009-04-02
CN101578129B (en) 2012-03-28
EP2228126A1 (en) 2010-09-15
EP2228126B1 (en) 2013-04-17
WO2008046779A1 (en) 2008-04-24
DE602007010505D1 (en) 2010-12-23

Similar Documents

Publication Publication Date Title
CN102553441B (en) Micro-dialysis device
Fissell et al. High-performance silicon nanopore hemofiltration membranes
EP1875957B1 (en) Plasma separation membrane
EP2943270B1 (en) A hollow fiber module having thin film composite- aquaporin modified membranes
JP5010026B2 (en) Hollow fiber capillary membrane and method for producing the same
EP0294737B1 (en) Polysulfone hollow fiber membrane and process for making the same
EP3013463B1 (en) Ceramic whole blood hollow fiber membrane filter medium and use thereof for separating blood plasma / serum from whole blood
CN109862957B (en) Method for determining the permeability properties of hollow fiber membranes
EP0842694A1 (en) Hollow yarn membrane used for blood purification and blood purifier
US6773591B2 (en) Bundle of hollow fibres for a device for extracorporeal treatment of blood and plasma, and process for its production
EP2845641A1 (en) Permselective asymmetric membranes with high molecular weight polyvinylpyrrolidone
CA2149418C (en) High flux hollow fiber membrane
Sakai et al. Formation of poly (methyl methacrylate) membranes utilizing stereocomplex phenomenon
CN113316481A (en) Dialyzer comprising fluorine-containing hollow fiber membranes
JP2002045662A (en) Permselective hollow fiber membrane
KR20230076840A (en) hemodialysis machine
JP2008259802A (en) Hollow fiber membrane and blood purifier incorporating the same
KR20010073727A (en) A polysulfone-based hollow fiber membrance for hemodialysis

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant